Aerosols are useful in a wide variety of applications. For example, it is often desirable to treat respiratory ailments with, or deliver medicaments by means of, aerosol sprays of finely divided particles of liquid and/or solid, such as powders, liquid medicaments, and the like, which are inhaled into a patient's lungs. Aerosols are also used for such purposes as providing desired scents to rooms, applying scents to the skin, and delivering paint and lubricant, for example.
Various techniques are known for generating aerosols, particularly in the field of medicine. For example, U.S. Pat. Nos. 4,811,731 and 4,627,432 both disclose devices for administrating medicaments to patients in which a capsule is pierced by a pin to release medicament in powder form. The user inhales released medicament through an opening in the device. Medicaments in liquid form are known to be delivered by generation of an aerosol with a manually operated pump. The pump draws liquid from a reservoir and forces it through a small nozzle opening to form a fine spray.
Both of these methods of generating an aerosol for the delivery of medicaments suffer from problems. The aerosols produced by these techniques contain substantial quantities of particles or droplets which are too large to be inhaled. Further, it is difficult to synchronize the inhalation of the medicament with the pumping of the aerosol device or the release of the powder. Persons who have difficulty in generating a sufficient flow of air through the device to properly inhale the medicaments, such as asthma or emphysema sufferers, have particular difficulty in using these devices.
An alternate means of delivering a medicament is generating an aerosol including liquid or powder particles by means of a compressed propellant, usually a chloro-fluoro-carbon (CFC) or methyl chloroform, which entrains the medicament, usually by the Venturi principle. Such inhalers are usually operated by depressing a button to release a short charge of the compressed propellant which contains the medicament through a spray nozzle, allowing the propellant encapsulated medicament to be inhaled by the user. However, it is again difficult to properly synchronize the inhalation of the medicament with depression of the actuator. Further, large quantities of medicament or other materials are not suitably delivered by this method. This method is better suited to delivery of such materials as antiperspirants, deodorants and paints, for example.
Most known aerosol generators also are unable to generate aerosols having an average mass median aerosol diameter (MMAD) less than 2 to 4 microns, and are incapable of delivering high flow rates, such as above 1 milligram per second, with particles in the range of 0.2 to 2.0 microns. A high flow rate and small particle size are particularly desirable for better penetration of the lungs during medicament administration, such as for asthma treatment.
Large particles generated by aerosol generators may be deposited in the mouth and pharynx of the patient, rather than inhaled into the lungs. Further, what is inhaled may not penetrate the lungs deeply enough. Therefore, it is known to add a spacer chamber to a pressurized inhaler mechanism in order to allow the propellant time to evaporate, decreasing the mass median aerosol diameter of the particles. See, for example, U.S. Pat. No. 5,855,202 to Andrade and Eur. Respir. J. 1997; 10:1345–1348. Particles from aerosol generators may have an MMAD of 5–6 μm. The use of a spacer chamber in such a case reduces the particle MMAD to about 1.5 μm or greater, enhancing medicament deposition in the lung as opposed to the mouth or throat. See, for example, Eur. Respir. J. 1997, 10:1345–1348; International Journal of Pharmaceutics, 1 (1978) 205–212 and Am. Rev. Respir. Dis. 1981, 124:317–320.
Spacer chambers also are known to affect the output of the aerosol device because of the static charge which may be created therein. Medicament particles may be deposited in spacer chambers by electrostatic attraction to the spacer chamber wall, by inertial impaction, or by gravitational settling over time. Further, different medicaments behave differently within such spacer chambers based on particle size, particle charge, and the like. Thus, loss of medicament occurs within spacer chambers and is a drawback to effective spacer chamber use. See Eur. Respir. J. 1997; 10: 1345–1348.
The aerosol generator (CAG) described in U.S. Pat. No. 5,743,251, herein incorporated by reference, and further described in Respiratory Drug Delivery VI, Eds. R. N. Dalby et al., Interpharm Press, IL (1998) pp 97–102, has many advantages over other aerosol generators. In general, the CAG operates by supplying a material in liquid form to a flow passage, such as a tube or capillary, and heating the flow passage so that the material volatilizes and expands out of the open end of the flow passage. The volatilized material combines with ambient air in such a manner that the volatilized material condenses to form an aerosol. The aerosol therefore contains no propellant, and has a mass median aerosol diameter of less than about 2 microns, generally between about 0.2 and about 2 microns, and preferably between about 0.2 and about 1 micron.
However, like other aerosol generators, some material can be lost during aerosol generation to the CAG device itself. It has been found that some aerosol particles can deposit on the end of the capillary or tube, thereby retaining the aerosol particles within the device itself. This phenomenon appears in part to be solute dependent. Further, if used to deliver medicament to the lungs of a patient, some aerosolized medicament can be lost to the throat and mouth of the patient. Because the CAG produces very fine particles, the particles may potentially be exhaled before settling fully into the patient's lungs, diminishing the amount of medicament delivered to the patient.
It is desirable to achieve a particle size of an aerosol which can penetrate deep into the lungs. It is further desirable to have the same or approximately the same mass median aerosol diameter for the aerosolized liquid and solid components. Further, it is desirable to minimize loss of the aerosol to the aerosol generator, as well as to the mouth and throat of the patient. One or more of these attributes can be achieved by the methods and apparatus described herein.